Dispersibility and surface properties of hydrocortisone-incorporated self-assemblies

Abstract

The ability of lipidic self-assembly systems to solubilize hydrophobic drugs allows for the enhancement of the delivery of poorly water-soluble drugs. Hydrophobic molecules are incorporated into the lipidic part of the self-assemblies, which alters their structure and surface properties, affecting their dispersibility. The effects of the incorporation of hydrophobic molecules on the structure of aqueous dispersions of amphiphiles should be precisely investigated. However little work has been done regarding the effects of drug incorporation on the surface and internal properties of lipidic self-assemblies. Herein, the effects of the incorporation of the hydrophobic drug, hydrocortisone (HC), on dispersions composed of monoolein (MO), oleic acid (OA), and Pluronic F127 (F127) are investigated. Via Raman spectroscopic analysis, HC was shown to be homogeneously distributed in the particles. This revealed that the incorporated HC had minimal effects on the lipid packing state in the self-assemblies. The HC-incorporated particles were dispersive for at least 24 h, although aggregation might happen after long incubation (couple of days). Cryogenic transmission electron microscopy images revealed particles with altered inner structure after HC incorporation. HC increased the size of the particles, suggesting that HC could reorganize the molecules in the dispersions. The absolute zeta potential values of the particles decreased by increasing the HC loading, suggesting an increased hydrophobicity of the HC-loaded particles. Laurdan fluorescence analysis revealed that the localized polarity of the dispersions turned to be more hydrophobic with increased HC concentrations. These results suggest that hydrophobic drugs, like HC, certainly influence the surface properties and inner structure of the self-assemblies, resulting in the changes in the particles’ dispersibility. The characterization method using fluorescent probe-based analysis and Raman spectroscopy is effective in revealing how the physicochemical properties of the self-assemblies contribute to understanding the dispersibility of nanocarriers encapsulating hydrophobic drugs.